Recent progress in optical voltage-sensor technology and applications to cardiac research: from single cells to whole hearts.

The first workshop on Novel Optics-based approaches for Cardiac Electrophysiology (NOtiCE) was held in Florence Italy in 2018. Here, we learned how optical approaches have shaped our basic understanding of cardiac electrophysiology and how new technologies and approaches are being developed and validated to advance the field. Several technologies are being developed that may one day allow for new clinical approaches for diagnosing cardiac disorders and possibly intervening to treat human patients. In this review, we discuss several technologies and approaches to optical voltage imaging with voltage-sensitive dyes. We highlight the development and application of fluorinated and long wavelength voltage-sensitive dyes. These optical voltage sensors have now been applied and well validated in several different assays from cultured human stem cell-derived cardiomyocytes to whole hearts in-vivo. Imaging concepts such as dual wavelength ratiometric techniques, which are crucial to maximizing the information from optical sensors by increasing the useful signal and eliminating noise and artifacts, are presented. Finally, novel voltage sensors including photoacoustic voltage-sensitive dyes, their current capabilities and potential advantages, are introduced.